Effectiveness of an enhanced antibiotic stewardship programme among paediatric patients in a tertiary hospital in Vietnam.

BACKGROUND: In 2016, the Vietnamese Ministry of Health promoted development of antimicrobial stewardship for hospitals. AIM: To evaluate the effectiveness and safety of the enhanced antibiotic stewardship programme (ASP) compared to the original ASP among paediatric patients at a tertiary hospital for infectious diseases in Vietnam. METHODS: An interrupted time-series analysis was conducted to examine antibiotic use in paediatric patients aged 0-17 years admitted to the Hospital for Tropical Diseases in Ho Chi Minh City from April 2016 to March 2020. Outcomes measured were defined daily doses (DDDs) per 1000 patient-days; antibiotic days of therapy (DOT) per 1000 patient-days; percentage of antibiotic use by the World Health Organization Access, Watch, and Reserve (AWaRe) system; Access-to-Watch ratio; and worse clinical outcomes at discharge. FINDINGS: Of 60,172 admissions during the study period, 28,019 received at least one antibiotic (46.6%) during hospital stay. The Watch antibiotics were the most frequently prescribed (78.1% of total antibiotic courses). The enhanced ASP did not improve antibiotic prescribing by DDDs per 1000 patient-days (risk ratio: 1.05; 95% confidence interval: 0.94-1.17) and DOT per 1000 patient-days (1.11; 0.99-1.25) compared to the original ASP. However, the percentage of Access antibiotics prescribed, and the Access-to-Watch ratio increased after the enhanced ASP (1.73; 1.38-2.17). There was no significant difference in worse clinical outcomes at discharge between the original and enhanced ASP (1.25; 0.78-2.00). CONCLUSION: The enhanced ASP had modest impact on antibiotic consumption in the paediatric population despite the improvement of Access antibiotic use and the Access-to-Watch ratio.

Histotype predicts the curative potential of radiotherapy: the example of ovarian cancers.

BACKGROUND: To explore the influence of ovarian cancer histotype on the effectiveness of adjuvant radiotherapy (RT). METHODS: A review of a population-based experience included all referred women with no reported macroscopic residuum following primary surgery who underwent adjuvant platin-based chemotherapy (CT), with or without sequential RT, and for whom it was possible to assign histotype according to the contemporary criteria. RESULTS: Seven hundred and three subjects were eligible, of these 351 received RT. For those with apparent stage I and II tumors, the cohort with clear cell (C), endometrioid (E), and mucinous (M) disease who additionally received RT exhibited a 40% reduction in disease-specific mortality and a 43% reduction in overall mortality. CONCLUSIONS: The curability of those with stage I and II C-, E-, and M-type ovarian carcinomas was enhanced by RT-containing adjuvant therapy. This benefit did not extend to those with stage III or serous tumors. These findings necessitate reassessments of the role of RT and of the nonselective surgical and CT approaches that have characterized ovarian cancer care.

Effect of increasing inclusion rates of tofu by-product in diets of growing pigs on nitrogen balance and ammonia emission from manure.

To reduce competition with human-edible feed resources, it is of interest to incorporate by-products from the food industry in animal feeds. The current research investigated the effect of including increasing amounts of tofu by-product (TF) in practical pig diets on animal performance, nitrogen balance and ammonia emissions from manure. Two experiments were conducted including a control diet without TF, containing 160 g/kg dietary non-starch polysaccharides (NSPs) and three diets including 122, 246 and 360 g TF/kg DM (TF122, TF246 and TF360, respectively) to reach 220, 280 and 360 g/kg NSP. All diets had the same level of CP and protein digestible in the small intestine which particularly was realized by replacing rice bran with TF. Animal performance was assessed in a first experiment with 40 growing barrows with initial BW of 26.6 ± 1.80 kg (M ± SD) being allocated to the 4 treatments, during 2 growth phases (i.e. until 50 kg BW and from 50 to 80 kg BW). In the growth phase until 50 kg, feed intake and average daily gain (ADG) were linearly reduced by dietary TF inclusion, while this negative impact disappeared during the second growth phase (50 to 80 kg BW). Tofu by-product inclusion even positively affected the feed conversion ratio during this second growth phase (3.4 to 2.7 kg feed/kg ADG for 0 to 360 g/kg dietary TF). Over the entire growth period, performance and feed intake were negatively affected at the highest dietary TF level. Experiment 2 was conducted to assess digestibility, nitrogen balance and ammonia emission from manure. For this purpose, 16 pigs with BW of 62.8 ± 3.6 kg (M ± SD) were assigned to either 1 of the 4 treatments. There was no difference in total tract apparent digestibility of dietary organic matter or CP, while NDF digestibility increased with increasing TF level, suggesting increasing importance of the hindgut fermentation when digesting diets with increasing TF levels. Nevertheless, this was not reflected in increasing levels of faecal volatile fatty acids or purines, nor in reduced manure pH. As a result, ammonia emission from slurry was not reduced through dietary TF inclusion, despite the linear decrease in urinary nitrogen. In conclusion, TF can be included in pigs' diets up to an inclusion rate of 25% without risk of impaired animal performance; however, this dietary strategy fails to mitigate ammonia emission from slurry.

Nanoparticle probes for quantifying supramolecular determinants of biosurface affinity.

Interactions between macromolecular systems and biosurfaces are complicated by both the complexity of these multivalent interactions and challenges in quantifying affinities. A library of gold nanoparticles (AuNPs) as multivalent probes is used to quantify biosurface affinity, using hair as a model targeted substrate.

Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia.

One of the best approaches to identifying genetic changes critical to oral cancer progression is to compare progressing and nonprogressing oral premalignant lesions. However, such samples are rare, and they require long-term follow-up. The current study used the large archive network and clinical database in British Columbia to study loss of heterozygosity (LOH) in cases of early oral premalignancies, comparing those with a history of progression to carcinoma in situ or invasive cancer and those without a history of progression (referred to as nonprogressing cases). Each of 116 cases was analyzed for LOH at 19 microsatellite loci on seven chromosome arms (3p, 4q, 8p, 9p, 11q, 13q, and 17p). The progressing and nonprogressing cases showed dramatically different LOH patterns of multiple allelic losses. An essential step for progression seems to involve LOH at 3p and/or 9p because virtually all progressing cases showed such loss. However, LOH at 3p and/or 9p also occurred in nonprogressing cases. Individuals with LOH at 3p and/or 9p but at no other arms exhibit only a slight increase of 3.8-fold in relative risk for developing cancer. In contrast, individuals with additional losses (on 4q, 8p, 11q, or 17p), which appeared uncommon in nonprogressing cases, showed 33-fold increases in relative cancer risk. In conclusion, analysis of LOH at 3p and 9p could serve as an initial screening for cancer risk of early premalignancies. Follow-up investigation for additional losses would be essential for predicting cancer progression.

Measuring and modelling pollution for risk analysis.

The great scale and complexity of environmental risk analysis offers major methodological challenges to those engaged in policymaking. In this paper we describe some of those challenges from the perspective gained through our work at the University of British Columbia (UBC). We describe some of our experiences with respect to the difficult problems of formulating environmental standards and developing abatement strategies. A failed but instructive attempt to find support for experiments on a promising method of reducing acid rain will be described. Then we describe an approach to scenario analysis under hypothetical new standards. Even with measurements of ambient environmental conditions in hand the problem of inferring actual human exposures remains. For example, in very hot weather people will tend to stay inside and population levels of exposure to e.g. ozone could be well below those predicted by the ambient measurements. Setting air quality criteria should ideally recognize the discrepancies likely to arise. Computer models that incorporate spatial random pollution fields and predict actual exposures from ambient levels will be described. From there we turn to the statistical issues of measurement and modelling and some of the contributions in these areas by the UBC group and its partners elsewhere. In particular we discuss the problem of measurement error when non-linear regression models are used. We sketch our approach to imputing unmeasured predictors needed in such models, deferring details to references cited below. We describe in general terms how those imputed measurements and their errors can be accommodated within the framework of health impact analysis.

A double-blind crossover trial of Oral Balance gel and Biotene toothpaste versus placebo in patients with xerostomia following radiation therapy.

Following therapeutic irradiation of the head and neck, patients with profound xerostomia have complaints associated with oral dryness, effects upon use of oral prosthesis, speech, and taste. In addition, xerostomia may lead to risk of oral infections and rampant demineralization of teeth. The use of topical Oral Balance gel and Biotene toothpaste (Laclede Professional Products, Gardena, CA) versus carboxymethylcellulose gel and commercial toothpaste applications was assessed in a 2-week double-blind, crossover design. The palliative effects of Oral Balance gel and Biotene toothpaste were superior to the effects of a placebo. No effect on oral colonization by Candida species and cariogenic oral microflora was seen with use of the topical agents.

Oral topical doxepin rinse: analgesic effect in patients with oral mucosal pain due to cancer or cancer therapy.

Oral mucositis is a treatment limiting toxicity of cancer therapy. The purpose of this study was to assess the impact of doxepin oral rinse in the management of oral mucosal pain in cancer patients. Forty-one cancer patients with oral mucosal pain were provided a solution of doxepin (0.5%) for oral rinsing. Oral pain was assessed prior to rinsing, and following rinsing for 4 h using a visual analogue scale (VAS). Adverse effects were recorded. Doxepin rinse resulted in a reduction of pain intensity of more than 50%, with pain relief extending for more than 3 h with pain not returning to baseline 4 h after rinsing. The rinse was tolerated by patients with mucosal damage, and had acceptable taste, and infrequent mucosal stinging with use. Some patients reported sedation after use, likely due to systemic absorption. The results of this single dose trial suggest that topical doxepin rinse has significant ability to provide clinically significant pain relief in patients with mucosal damage with an extended duration of effect.

Impact of localized treatment in reducing risk of progression of low-grade oral dysplasia: molecular evidence of incomplete resection.

Currently, there is no consensus on the appropriate treatment for low-grade oral dysplasia. This is mainly due to the difficulty in predicting outcome for this heterogeneous group of lesions. In this study, we constructed a detailed clinical history of 66 mild and moderate dysplasias in order to determine how treatment affected outcome, and to evaluate the effect of treatment on lesions with different genetic profiles, which are defined by patterns of loss of heterozygosity (LOH) associated with low, intermediate and high risk of progression [Clin. Cancer Res., 6, 357-62, 2000]. The results showed that although treatment guided by clinical removal of leukoplakia reduced cancer progression risk in all three risk groups, the amount of reduction in our study group did not reach statistical significance. To assess whether completeness of lesion removal was a major factor in recurrence, repeat biopsies at the primary sites were analyzed for persistent LOH status on chromosomes 3p, 4q, 8p, 9p, 11q, 13q and 17p. Strikingly, eight of 17 cases judged clinically removed contained the same molecular clones in the initial and subsequent biopsies, suggesting incomplete removal. When molecular information was included in the assessment of lesion removal, treatment significantly reduced the risk of progression for cases with intermediate (P=0.043) and high risk (P=0.001) genetic profiles, but not cases with low-risk profiles. A 9.1-fold decrease in progression risk was observed for those with high-risk profile. Altogether, these data suggest the use of molecular profiles to guide the treatment of low-grade dysplasia. Our data also suggest that currently an inadequate margin may in part be responsible for the high rate of recurrence, especially in high-risk lesions.

Identification of occupational cancer risks in British Columbia. A population-based case-control study of 995 incident breast cancer cases by menopausal status, controlling for confounding factors.

Lifetime occupational histories as well as information on known and suspected breast cancer risk factors were collected by means of a self-administered questionnaire from 1018 women with incident breast cancer ascertained from the British Columbia Cancer Registry, and from 1020 population controls. A matched case-control study design was used. Conditional logistic regression for matched sets data and the likelihood ratio were used in a two-step procedure and were performed separately for pre-menopausal women, post-menopausal women, and for all cases combined. Excess risk was noted for several white-collar occupations. Significantly increased risk was observed: (1) among pre-menopausal women: in electronic data-processing operators; barbers and hairdressers; in sales and material processing occupations; and in the food, clothing, chemical and transportation industries; (2) among post-menopausal women: in schoolteaching; in medicine, health, and nursing occupations; in laundry and dry-cleaning occupations; and in the aircraft and automotive, including gasoline service station, industries. Several significant associations were also seen in the combined group of pre- and post-menopausal women, particularly in crop farmers and in the fruit and vegetable, publishing and printing, and motor vehicle repair industries. The results of this study suggest excess breast cancer risk in a number of occupations and industries, notably those that entail exposure to solvents and pesticides.

Identification of occupational cancer risks in British Columbia. Part II: A population-based case-control study of 1516 Prostatic cancer cases.

We have, as part of a program aimed at detecting occupational risk factors in British Columbia, collected lifetime occupational histories from 15,643 incident cancer cases, of whom 1519 had a diagnosis of prostate cancer. Occupational risks for this cancer site are examined using this large data set, and the results are presented in this report.

Identification of occupational cancer risks in British Columbia. Part I: Methodology, descriptive results, and analysis of cancer risks, by cigarette smoking categories of 15,463 incident cancer cases.

To identify occupational cancer risk factors, lifetime occupational, smoking, and alcohol-consumption histories were collected by means of a self-administered questionnaire from 15,463 male cancer patients aged 20 years and over as ascertained from the British Columbia population-based cancer registry; all cases were histologically confirmed. The study methodology, descriptive results, and cancer risks from cigarette smoking are reported. Assessment of questionnaire validation and reliability showed very high correlations between all variables analysed. Non-response bias, assessed among 221 non-responders and 432 matched controls, revealed no statistically significant differences for smoking status, education, or for 11 usual (longest-held job) occupational groups, except for managerial occupations and for four pooled groups that represented 6.7% of all occupations. Except for pancreatic cancer, a significant relationship was found for all cancer sites known to be strongly associated with cigarette smoking.

Cohort cancer incidence among pulp and paper mill workers in British Columbia.

OBJECTIVES: A study was conducted to investigate cancer risks in a cohort of pulp and paper workers. METHODS: All male workers with > or =1 years of employment in 14 pulp and paper mills in 1950-1992 were studied. Standardized incidence ratios (SIR) were used to compare the cancer incidence of the cohort with that of the Canadian male population. Record linkage with the National Cancer Registry was performed using the generalized iterative record linkage method. RESULTS: Altogether 1756 cancer cases were observed in the entire cohort. For > or =15 years of work, the entire cohort had significantly increased SIR values for pleural and prostate cancer and skin melanoma; there was also a significantly increased risk for skin melanoma among workers in the kraft process only, rectal cancer among workers in the sulfite process only, and stomach and prostate cancer and all leukemias combined among workers in both the kraft and sulfite processes. A separate analysis comparing workers in pulping and papermaking with those in the pulping process only did not reveal any difference in cancer risk and hence did not modify the results. The SIR values for skin melanoma were not significantly increased in a comparison using the British Columbia male population. Nine of 10 pleural cancers were mesotheliomas, which likely reflect past asbestos exposure. CONCLUSIONS: The results suggest that long-term work in the pulp and paper industry is associated with excess risks of prostate and stomach cancers and all leukemias for work in both kraft and sulfite processes and of rectal cancer for work in the sulfite process only.

Characteristics of oral and paraoral malignant lymphoma: a population-based review of 361 cases.

BACKGROUND: Lymphoma is the second most common neoplasm of the head and neck; almost 50% of all lymphomas occur in this region. Waldeyer's ring is the most common site of lymphomas involving the oral region. The purpose of this study was to review the characteristics of a large series of malignant lymphoma of the oral region. METHODS: Three hundred sixty-one consecutive cases of malignant lymphoma of the oral region were identified in the Tumor Registry between 1969 and 1998. RESULTS: The 361 cases (200 males and 161 females) of malignant lymphoma of the oral region accounted for 3.5% of all oral malignancies. The mean age was 62.5 years and the most prevalent site of involvement was the tonsil (32.7%), followed by the parotid gland (16.1%). Sixty-five percent of the lesions were diagnosed as large-cell (38%) or small-cell (27%) lymphoma. One quarter of the patients died of the disease in a mean of 2.78 years after diagnosis. Of a total 26 patients who died from other causes, 12 died because of other cancers, including 7 (27%) with leukemia and 5 (19%) with oral carcinoma. The prognosis is based, at least partially, on the histologic grading (low, intermediate, or high) and the anatomic stage of the disease. Localized low-grade lymphomas have a more favorable prognosis compared with those that are disseminated and/or have high-grade cellular changes. CONCLUSION: Lymphoma is the second most common malignant oral disease. Thorough head and neck and oral examination is necessary to identify lesions that may represent lymphoma.

A survey of antibiotic use in dentistry.

BACKGROUND: Antibiotics are important in the management and prophylaxis of infection in patients at risk of experiencing microbial disease. As a result of the increase in antimicrobial resistance, the authors conducted a survey to assess current antibiotic use in dental practice. METHODS: The authors mailed a two-page, pretested survey to all licensed dental practitioners in British Columbia, Canada. A total of 2,542 surveys were mailed; 19.9 percent were returned by fax or mail. The authors examined an association between factors analyzed using a chi 2 test. RESULTS: Respondents were demographically consistent with all registered dentists in British Columbia. They reported writing an average of 4.45 prescriptions per week. Antibiotics prescribed after treatment primarily were penicillin and its derivatives. Recommended adult doses of penicillin were prescribed by 59.2 percent of respondents; recommended daily doses of amoxicillin were prescribed by 72.2 percent of respondents. The average prescription duration was 6.92 days. Respondents prescribed prophylactic antibiotics an average of 1.15 times per week for prophylaxis of bacterial endocarditis; 17.5 percent reported postoperative dosing for prophylaxis, ranging from a one- to seven-day prescription with an average of 6.91 postoperative doses. Preoperative antibiotics were prescribed for patients with a history of rheumatic fever or any heart murmur or prosthetic hip. Antibiotics were prescribed more frequently for surgical procedures and patients with acquired immunodeficiency syndrome than for other circumstances. CONCLUSIONS: More than 80 percent of respondents reported that they followed current American Heart Association prophylaxis guidelines. The authors, however, noted discrepancies in prophylactic use of antibiotics for bacterial endocarditis and for patients with large joint prostheses, as well as in prescribing antibiotics in the presence of clinical infection. In therapeutic use, approximately 85 percent of respondents followed appropriate prescription guidelines for dosing and duration of therapy. CLINICAL IMPLICATIONS: Appropriate and correct use of antibiotics is essential to ensure that effective and safe treatment is available and that practices that may enhance microbial resistance are avoided. To improve standards of care, dentists need up-to-date pharmacology in dental education, as well as continuing education, further outcome studies and continuous assessment of dental practices.

Assessing viral retention and elimination in rotary dental instruments.

The authors of this article used a laboratory model of herpes simplex virus infection to assess the potential for contamination of dental handpieces by a human viral pathogen. They found that although all the handpieces in the study were fitted with anti-retraction valves, it was not until the units were flushed internally and disinfected externally that the pathogens were eliminated.

Compliance with fluoride gel use in irradiated patients.

Patients who undergo radiation therapy that includes the salivary glands frequently experience severe xerostomia. The standard of care for these patients who have natural teeth has become daily application of fluoride by means of custom-fabricated carriers. The purpose of this study was to determine patient compliance with fluoride gel application using carriers. Using a structured verbal questionnaire, we interviewed 76 patients who had completed radiation therapy for head and neck cancer. Thirty of these patients were seen regularly in the dental clinic of the Cancer Agency (group 1); the remaining 46 were not seen on a regular basis (group 2). Overall, 43% of patients reported using fluoride gel regularly (once a day). In group 1, 67% of patients used fluoride regularly, as did 28% of patients in group 2 (p = 0.001). There were no significant differences between the groups in frequency of toothbrushing and use of dental floss. Compliance with the use of fluoride in carriers was not associated with differences in other oral care measures in the two groups, which suggests that fluoride application in carriers achieves limited compliance in relation to daily oral health care measures. Regular follow-up of patients after radiation therapy is needed to assess their need for, and compliance with, daily fluoride application.

Novel mechanism of rapamycin in GVHD: increase in interstitial regulatory T cells.

Rapamycin (RAPA) is an immunosuppressive drug that prevents and treats graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT). One possible mechanism for its efficacy is induction of tolerance, through increased number or enhanced survival of regulatory T cells. In our experiments, B10.D2 BM and splenocytes were injected into lethally irradiated BALB/cJ recipients. The mice received i.p. injections of either RAPA or vehicle control on days 1-28. There was a significant survival advantage in RAPA-treated mice. Evaluation of the skin biopsies showed a dense cellular infiltrate in RAPA-treated mice. Further characterization of these cells revealed a higher percentage of regulatory T cells characterized by FoxP3-positive cells in high-dose RAPA-treated mice as compared with controls on day 30. This effect appears to be dose dependent. When peripheral blood analysis for FoxP3-positive cells was performed, there was no significant difference observed in the RAPA-treated mice as compared with control mice. These data show a novel mechanism of rapamycin in GVHD, accumulation of regulatory T cells in the GVHD target tissue: the skin.

From expert-based to quantitative retrospective exposure assessment at a Soderberg aluminum smelter.

OBJECTIVES: Expert judgement of exposure levels is often only poorly or moderately correlated with directly measured levels. For a follow-up of a historical cohort study at a Söderberg aluminum smelter we updated an expert-based semiquantitative job exposure matrix of coal tar pitch volatiles (CTPV) to quantitative estimates of CTPV and benzo(a)pyrene (BaP). METHODS: Mixed effects models to predict exposure for potroom operation and maintenance jobs were constructed from personal CTPV and BaP measurements. Mean exposures of jobs in non-potroom locations were directly calculated when measurements were available. Exposure estimates for jobs/time periods with no measurements were based on proportion of time spent in exposed areas compared to jobs where exposure was modeled or measured. For pre-1977, the original expert exposure assignments were calibrated using the updated 1977 estimates. RESULTS: The rate of change in exposure levels varied by time period and was accounted for in mixed models with a linear spline time trend. Other variables significant in the models were job, potroom group and season as fixed effects, and worker as a random effect. The models for potroom operations explained 45 and 27% of the variability in the CTPV and BaP measurements, respectively. The models for maintenance jobs explained 40 and 19% of the variability in the CTPV and BaP measurements, respectively. For 1977-2000 model estimates, direct calculation of means and extrapolation from modeled/measured exposures accounted for 57, 6 and 37% of the exposed person-years, respectively. CONCLUSIONS: The above methodology maximized the use of exposure measurements and largely replaced the original expert-based estimates. Finer discrimination between exposure levels was possible with the updated exposure assessment. The new estimates are expected to reduce exposure misclassification and help better assess the exposure-response relationships.

Incidence and spectrum of non-Hodgkin lymphoma in Chinese migrants to British Columbia.

The incidence and spectrum of non-Hodgkin lymphoma (NHL) differ between the Chinese and Caucasian populations. Using population-based registries, we studied the pattern of NHL in Chinese migrants to British Columbia (BC). The records of all NHL cases of Chinese descent diagnosed between 1980 and 1997 were retrieved. Age-standardized incidences were calculated by 5-year intervals in terms of age and calendar years and the relative rates were compared between the migrant, Hong Kong and BC populations. The histological distribution of NHL was compared with 4500 consecutive NHL cases diagnosed in the two populations. A total of 211 cases of migrant NHL were identified, with an age-standardized incidence rate of 7.11 per 100 000 per year, compared with the Hong Kong and BC rates of 7.91 [standardized incidence ratio (SIR) = 0.86, P = 0.01] and 11.88 (SIR = 0.56, P < 0.01). The standardized rates of follicular lymphoma remained low, but the incidence of gastric and nasal natural killer/T lymphomas in migrants were lower than expected. Genetic factors appeared to be stronger than environmental factors in governing the overall incidence of NHL in Chinese. However, certain subtypes of lymphoma may show decreased rates in migrants because of environmental factors.